This research will continue to characterize the process of oral immunization, one of the ways newborn mammals become immunized against environmental antigens. The lymphocytes of the gut-associated lymphoid tissues will be examined as the probable site of both local and circulating antibody production. The effect of antigen ingestion on the function of antigen specific T-helper and T-suppressor cells will be examined now that our oral immunization system has been adapted to the mouse. The principles of oral immunization have been adapted to the oral administration of diphtheria toxin. Animal experiments show that this method is safe and results in detectable immunity. After further characterization, these findings will be used to develop a model system for human disease prophylaxis by the use of formula additives. Breast milk antibody in orally immunized animals are being characterized and the effect on the newborns response to ingested antigens is being studied. Antisera from normal and milk tolerant infants will be compared to learn if internal determinants exposed by digestion are recognized by either group. The failure of orally immunized adult rabbits to recognize internal determinants appears to be related to the variable action of pepsin. The difference between normal and intolerant infants may be that intolerant infants digest the antigen more uniformly resulting in immunozation to new determinants. The antibodies and circulating antigen reactive cells against purified milk proteins present in both groups of infants will be compared. The long term goals are to characterize the normal immunologic responses of the newborn, identify deviations from the normal which may be associated with disease, and provide a more acceptable, more widely applicable method for the immunization of newborns against bacterial toxins.